The work proposed for the current year is to examine the diminished maternal bone marrow derived B-lymphocyte (B-cell) responsiveness and to determine the incidence of the serum lymphocyte inhibitors during pregnancy. The peripheral blood lymphocytes from pregnant women and non- pregnant control individuals were purified using a ficoll-hypaque (F/H) density gradient and cultured in medium containing 20% plasma from a normal individual. Pregnant donor's lymphocytes were 30 to 80% less responsive to pokeweed mitogen (PWM a thymus-derived T-cell and B-cell mitogen) stimulation than those of the controls. In a search for pure human B-cell mitogen, a calf fetal protein, fetuin, and, unexpectedly, F/H treatment of lymphocytes were both found to stimulate solely B- cells. Both fetuin and F/H treatment were found to induce appreciably less lymphocyte response in pregnant donors than in control individuals. The results thus far appear to confirm our preliminary finding which indicates the presence of B-cell hyporesponsiveness during pregnancy. In the study of lymphocyte inhibitors, the pregnant women's sera were shown to inhibit lymphocyte responses to PWM or allogeneic lymphocytes. The results were interpreted to indicate the presence of different inhibitors for lymphocytes responding to different mitogens